This proposal is directed toward a genetic analysis of adult seropositive rheumatoid arthritis (RA) in negroid and caucasoid families. The genetic markers being used for establishing genetic linkage of the RA susceptibility gene(s) with HLA are the "defined" alloantigens dictated by the HLA-A, B, C and DRw-loci within the major histocompatibility complex on chromosome 6. Two types of families will be studied: one type, termed simplex families, will be characterized by the presence of only one seropositive RA in a three generation span of first-degree relatives; the second type, termed multiplex families, consist of two or more RA's within a three generation span of first-degree relatives. The data will be analyzed for genetic linkage using the LIPED and GEOPED computer programs. The information will be useful in determining the mode of inheritance of RA and may serve as a means of defining sub-types of RA. In addition, this project involves the screening of "undefined" B-cell alloantisera for reactivity against B-cells obtained from the family members described above and against a random series of RA's treated at the UAB Rheumatology Clinics. There have been several reports describing the value of this procedure for the identification of disease specific cell surface markers. B-cell alloantisera found to react with an increased frequency against RA's compared to controls will be used to study the families as means of determining patterns of segregation and possibly to use these antigens in the linkage analysis.